The long term objectives of this project are to understand the mechanisms that contribute to the decline in airway reactivity between infancy and adolescence, and the presence of heightened airway reactivity in infants and older children following lung injury early in life. Normal infants and adult asthmatics demonstrate greater maximal airway narrowing in response to bronchoconstrictors than do normal adults. Mechanical forces in the airways and the lung parenchyma, and the interdependence between these forces, are significant determinants of the decrease in airway caliber that occurs in response to bronchoconstrictors. We hypothesize that the balance between these forces change with the maturation of the lung, and that an alteration of these forces early in life results in heightened airway reactivity in older children and adults. The specific aims of this project are 1) to determine the extent of age-related differences in the responses of airway resistance and tissue resistance to methacholine using an animal model, 2) to compare airway-parenchymal interdependence in the immature and mature animal, 3) to determine the effects of parenchymal lung injury early in life on airway reactivity in the mature animal, and 4) to compare the static and the dynamic contractile properties of immature and mature rabbit airway smooth muscle. An alveolar capsule technique will be used to partition pulmonary resistance into airway and tissue components. Physiologic measurements in mature and immature animals will be correlated with morphometric assessments of airway caliber, airway wall thickness, quantity of airway smooth muscle, elastin, and alveolar size and shape. Airway-parenchymal interdependence will be evaluated through physiologic and morphometric assessments of airway narrowing at different lung volumes. Parenchymal injury in the immature animal will be produced with intra-tracheal elastase and collagenase, and when the animals are mature, physiologic and morphometric measurements will be obtained.